Aksimentiev Aleksij, Heng Jiunn B, Timp Gregory, Schulten Klaus
Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
Biophys J. 2004 Sep;87(3):2086-97. doi: 10.1529/biophysj.104.042960.
We have previously demonstrated that a nanometer-diameter pore in a nanometer-thick metal-oxide-semiconductor-compatible membrane can be used as a molecular sensor for detecting DNA. The prospects for using this type of device for sequencing DNA are avidly being pursued. The key attribute of the sensor is the electric field-induced (voltage-driven) translocation of the DNA molecule in an electrolytic solution across the membrane through the nanopore. To complement ongoing experimental studies developing such pores and measuring signals in response to the presence of DNA, we conducted molecular dynamics simulations of DNA translocation through the nanopore. A typical simulated system included a patch of a silicon nitride membrane dividing water solution of potassium chloride into two compartments connected by the nanopore. External electrical fields induced capturing of the DNA molecules by the pore from the solution and subsequent translocation. Molecular dynamics simulations suggest that 20-basepair segments of double-stranded DNA can transit a nanopore of 2.2 x 2.6 nm(2) cross section in a few microseconds at typical electrical fields. Hydrophobic interactions between DNA bases and the pore surface can slow down translocation of single-stranded DNA and might favor unzipping of double-stranded DNA inside the pore. DNA occluding the pore mouth blocks the electrolytic current through the pore; these current blockades were found to have the same magnitude as the blockade observed when DNA transits the pore. The feasibility of using molecular dynamics simulations to relate the level of the blocked ionic current to the sequence of DNA was investigated.
我们之前已经证明，纳米厚的金属氧化物半导体兼容膜中的纳米直径孔隙可作为检测DNA的分子传感器。人们正在积极探索使用这类设备进行DNA测序的前景。该传感器的关键特性是DNA分子在电解液中通过纳米孔跨膜的电场诱导（电压驱动）易位。为了补充正在进行的关于开发此类孔隙并测量DNA存在时响应信号的实验研究，我们对DNA通过纳米孔的易位进行了分子动力学模拟。一个典型的模拟系统包括一片氮化硅膜，将氯化钾水溶液分隔成两个由纳米孔连接的隔室。外部电场促使溶液中的DNA分子被孔隙捕获并随后发生易位。分子动力学模拟表明，在典型电场下，20个碱基对的双链DNA片段可在几微秒内穿过横截面为2.2×2.6 nm²的纳米孔。DNA碱基与孔隙表面之间的疏水相互作用会减缓单链DNA的易位，并可能有利于双链DNA在孔隙内解链。堵塞孔口的DNA会阻断通过孔隙的电解电流；发现这些电流阻断与DNA通过孔隙时观察到的阻断幅度相同。我们研究了使用分子动力学模拟将阻断离子电流水平与DNA序列相关联的可行性。
